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Biofilm-infected wounds remain a major clinical challenge because biofilm infections and persistent inflammation impede the ability of traditional therapies to adapt dynamically to the constantly changing wound microenvironment. Here, a successful development of an intelligent hydrogel dressing (HCOC) has been achieved by integrating ultrasmall mixed-valent copper nanozymes (Cu5.4O) encapsulated in humic acid (HAs) into an oxidized alginate-chitosan network, enabling programmed and pH-responsive treatment. During the acidic biofilm infection stage (pH < 6.5), the shells of HAs aggregate, allowing for the controlled release of Cu5.4O to initiate chemodynamic therapy (CDT), while also enabling HAs-mediated photothermal therapy (PTT). This synergistic CDT/PTT achieves remarkable antibacterial efficacy, eliminating 99.99% of methicillin-resistant Staphylococcus aureus and Escherichia coli, and dispersing 87.46% of the biofilm. As the pH of the infected wound increases (pH ≥ 7.0), HAs dissolve, releasing more Cu5.4O nanozymes, which switch to a potent antioxidant mode - > 90% of reactive oxygen species - and promote M2 macrophage polarization by inhibiting NF-κB and activating Wnt/β-catenin signaling. In vivo, HCOC combined with near-infrared irradiation accelerates wound healing in infected wounds, achieving a 91.65% closure rate within 7 days, significantly enhancing angiogenesis (approximately 90 CD31 + cells per field), and enhancing M2 macrophage infiltration (approximately 110 CD163 + cells per field). This study establishes a paradigm-shifting platform for precise trauma management through microenvironment-responsive sequence therapy. This research was published in Bioactive Materials under the title "Smart microenvironment-adaptive nanocatalytic hydrogel for sequential antibacterial, anti-inflammatory and regenerative therapy of biofilm-infected wounds".
Reference Information:
DOI: 10.1016/j.bioactmat.2026.02.043
